Table 1.
The role of IEXs in the pathogenesis of various diseases
| Exosome source | mediator | Target cell | Mediator target | Type of disease | Result |
|---|---|---|---|---|---|
| M2 macrophages | miR-221-3p | Tumor cells | Cyclin-dependent kinase inhibitor 1B | Tumor | Resolve the cell cycle arrest in the G1/S and help tumor cells proliferation |
| M2 macrophages | miR-29a-3p and miR-21-5p | TCD4+ cells | STAT3 | Tumor |
1. These exosomes disrupt the Treg/Th17 balance 2. ↓ Inflammatory cytokines production such as IL4, IL6, and TNF-a 3. ↑ Anti-inflammatory cytokines production like IL10 |
| M2 macrophages | miR-21-5p and miR-155-5p | Tumor cells | Brahma-related gene 1 (BRG1) | Tumor | ↑ Colon cancer cells’ migration and metastasis |
| Monocyte-derived macrophages | miR-223 | Tumor cells | Myocyte-enhancing factor-2c (Mef-2c) | Tumor |
1. ↑ β-catenin nuclear accumulation 2. ↑ Breast cancer cells’ migration and metastasis |
| M2 macrophages | Apolipoprotein E (ApoE) | Tumor cells | PI3K/Akt/mTOR signaling pathway | Tumor | ↑ Gastric cancer cells’ migration and metastasis |
| Myeloid-derived suppressor cells (MDSCs) | Fas-L (CD95L) | TCD8+ cells | Fas (CD95) | Tumor | Induce activation-induced apoptosis (AICD) in TCD8+ cells |
| M2 macrophages, Dendritic cells (DCs), and T lymphocytes | miR-21 | Tumor cells | APAF1, PTEN, PDCD4, and P21 | Tumor |
1. ↓ Caspases 9 and 3 activations and apoptosis initiation 2. ↑ Drug resistance in cancer cells |
| M2 macrophages | non-coding RNA that stabilizes HIF-1α (HISLA) | Tumor cells | Hypoxia-inducible factor 1-alpha (HIF-1α) | Tumor |
1. Inhibits hydroxylation and degradation of HIF-1α 2. ↑ Aerobic glycolysis and enhanced resistance to apoptosis in cancer cells |
| DCs | MHC-I and II | Alloreactive T cells | N/A | Tissue transplant rejection | Stimulate the anti-alloantigen responses |
| DCs and macrophages | leukotriene A4 (LTA4), LTB4 and LTC4 | Immune cells, especially neutrophils | N/A | Asthma and allergic diseases | ↑ Inflammation by attracting other immune cells |
| Thymic stromal lymphopoietin (TSLP)-activated DCs | OX40-L | TCD4+ cells | OX40 | Asthma and allergic diseases |
1. ↑ TCD4+ cells differentiation to Th2 2. ↑ IgE production |
| Mast cell | CD40L |
B lymphocytes, T lymphocytes, bronchial smooth muscle cells (BSMCs) |
CD40 | Asthma and allergic diseases |
1. Stimulate IgE production 2. Stimulate the production of pro-inflammatory cytokines |
| HTLV-1 infected T lymphocytes | Tax proteins and viral mRNAs such as Tax, HBZ, and Env | Different types of host cells | Activate the NF-κB, and Akt pathways, stimulating ROS production | Infectious diseases |
1. ↑ Infected cell survival 2. Contribute to the spread and pathogenesis of HTLV-1-induced disease 3. Disrupts DNA repair mechanisms |
| T lymphocytes | miR-155, miR-142-5p, and miR-142-3p | Pancreatic beta cells | Regulate the NF-κB related signaling pathway | Type 1 diabetes | ↑ Secretion of CCL2, CCL7, and CXCL10 and apoptosis in pancreatic beta cells |
| Adipose tissue-derived macrophages | N/A | Macrophages | Reduce the insulin-dependent phosphorylation of Akt by increasing NF-κB activation | Type 2 diabetes |
1. ↓ The transfer of GLUT4 to the cell surface 2. Blocks glucose uptake 3. Stimulating M1 macrophage differentiation |
| M1 macrophages | N/A | TCD4+ cells and CD8+ T cells | Regulate the T-bet transcription factor activity | Guillain-Barré syndrome |
1. ↑ Th1 cells responses 2. ↑ The ratio of IFN-γ and IL-17 producing CD4+ T cells |
| T lymphocytes | miR-326 | Inhibit Ets-1 and CD47 expression | TCD4+ cells, monocytes, brain resident cells | Multiple Sclerosis |
1. ↑ Th17 differentiation in vitro and in vivo 2. ↑ ICAM-1 and Mac-1 (macrophage-1 antigen) expression in monocytes 3. ↑ Phagocytic activity of macrophages |
ICAM-1 Intercellular adhesion molecule 1, APAF1 Apoptotic peptidase activating factor 1, PTEN Phosphatase and tensin homolog, NF-κB Nuclear factor-kappa B, NK cell Natural killer cells, TNF-α Tumor necrosis factor-alpha, IL Interleukin, MCP-1 Monocyte Chemoattractant Protein-1, OVA Ovalbumin, MHC Major histocompatibility complex, TLR Toll-like receptor, AchR Acetylcholine receptor, TGF-β1 Transforming growth factor-beta 1, N/A Not applicable